[unreadable] The availability of an accurate and objective surrogate biomarker of the vascular complications associated with the development and progression of diabetic retinopathy would substantially improve the diagnosis and management of this major cause of visual impairment or blindness. The purpose of this research project is to determine whether the functional MRI (fMRI) measurement of the retinal oxygenation to a hyperoxic inhalation challenge can be used to predict risk, improve early diagnosis, monitor the progression of the microvascular complications of diabetic retinopathy and assess treatment efficacy in patients with Type I diabetes mellitus with varying degrees of retinopathy. Previous fMRI studies in animal models of diabetes, as well of studies of retinal blood flow in diabetic patients, suggest that the retinal oxygenation response to a hyperoxic challenge will be subnormal in patients with diabetes. However, it has not been possible to test this hypothesis in human subjects because adequate technologies were not available until recently. However, with an innovative fMRI technique it is now possible to accurately measure the retinal oxygenation to a hyperoxic challenge in humans. Consequently, it is now plausible to suggest that an fMRI measure of the retinal oxygenation response will provide a physiological surrogate endpoint that can be used to predict risk, improve early diagnosis, assess treatment efficacy and monitor the progression of the microvascular complications of diabetic retinopathy. The principal objective of this proposal is to test the specific hypotheses that i) the fMRI retinal oxygenation response to a hyperoxic challenge is significantly reduced in patients with Type I diabetes and ii) this response becomes increasingly subnormal as the degree of diabetic retinopathy increases in severity. To accomplish this objective fMRI will be used to measure the retinal oxygenation response as a function of the degree of retinopathy in patients with diabetes and contrast it with the response obtained from normal human volunteers of similar age. This will provide, for the first-time, direct information about oxygenation of the retina in human diabetics. The results of this proposed study may aid in the early diagnosis and staging of diabetic retinopathy as well as in the development and application of rational prevention and treatment strategies. [unreadable] [unreadable] [unreadable]